A Pilot Study to Test the Feasibility for a Randomized Controlled Trial of E-cigarettes as Harm Reduction Tools Among People Who Smoke and Previously Failed to Quit with Pharmacotherapy.

INTRODUCTION: We conducted a pilot study to test the feasibility of a future randomized controlled trial comparing e-cigarettes to traditional pharmacotherapy among people who smoke daily, were motivated to quit, and failed to quit within the past 5 years using pharmacotherapy. METHODS: Eligible participants were assigned to either: 1) an e-cigarette (n=20) or 2) combination nicotine replacement therapy (patches and lozenges) (n=10). Participants received 5 weeks of product and selected a quit date 1 week later. Assessments were completed weekly, and electronic diaries were completed each day. As a pilot randomized controlled trial, outcomes focus on effects sizes and not statistical significance. RESULTS: Participants in the e-cigarette and NRT groups had a mean age of 51 (SD=13) and 50 (SD=10) years old, were 55% and 60% female, and were 15% and 0% non-white, respectively. At least 90% of participants completed each weekly assessment, and 77% of participants completed at least 80% of daily diaries. Mean cigarettes smoked per day reduced from 18 (SD=6.2) to 2.4 (SD=4.4) per day in the e-cigarette group and 16.5 (SD=8.5) to 4.9 (SD=5.9) per day in the NRT group. Rates of biochemically confirmed 7-day point prevalence abstinence at the end of treatment were numerically, but not statistically, higher in the e-cigarette group than the NRT group (35% vs. 10%, OR=4.8, 95% CI=0.5-46.5). CONCLUSIONS: Among current daily cigarette smokers who have previously tried to quit and failed using standard pharmacotherapies, provision of an e-cigarette is a feasible intervention. A larger adequately powered trial is warranted. IMPLICATIONS: This pilot study suggests that e-cigarettes may serve as an acceptable harm reduction intervention for people who smoke who cannot quit smoking with traditional pharmacotherapy, but adequately powered randomized controlled trials are needed.

A National Dental Practice-Based Research Network phase II, cluster-randomized clinical trial assessing nicotine replacement therapy sampling in dental settings: study protocol for the Free Samples for Health (FreSH) study.

BACKGROUND: Cigarette smoking has major detrimental effects on oral health. Tobacco interventions in dental settings are effective, but rarely delivered. The American Dental Hygienists Association recommends that oral health providers: Ask patients about tobacco use, Advise quitting tobacco use, and Refer to state quitlines (Ask-Advise-Refer; AAR). While AAR connects patients to counseling, it does not directly connect patients to medication. Nicotine replacement therapy sampling (NRTS) is an empirically supported intervention to provide starter packs of nicotine replacement therapy (NRT) to people who smoke. NRTS combined with AAR could be an effective tobacco treatment intervention for dental settings. METHODS: This manuscript describes the study protocol for the Free Samples for Health (FreSH) study, a group randomized clinical trial testing the effectiveness of NRTS + AAR vs. AAR alone on long-term smoking abstinence. Fifty dental practices in the Midwest and Northeast nodes of the National Dental Practice-Based Research Network are randomly assigned to provide AAR and either a 2-week supply of 14-mg nicotine patches and 4-mg nicotine lozenges (NRTS condition) or an electric toothbrush (ET condition). Approximately 1,200 patients who currently smoke-regardless of interest in quitting- are recruited during dental visits. Participants complete a baseline survey in-person, then after visit, 1-, 3-, and 6-month follow-up surveys remotely. The primary outcome is carbon monoxide-confirmed 7-day point prevalence abstinence from combustible tobacco measured at 6 months post-enrollment. Secondary outcomes include: 24-h intentional quit attempts, change in cigarettes smoked per day, NRT utilization, attitudes toward NRT, intention to use NRT, and intention to quit smoking. A key informant process evaluation and cost effectiveness analysis will provide information for future implementation of NRTS. DISCUSSION: This is the first clinical trial to assess the effectiveness of NRTS on promoting smoking cessation in dental settings. If effective, this treatment could be implemented to increase the provision of smoking cessation interventions in dental settings to provide an additional treatment access point for people who smoke. TRIAL REGISTRATION: Registered at ClincalTrials.gov (NCT05627596) on 11/25/2022.

CHRNA5-A3-B4 and DRD2 Genes and Smoking Cessation Throughout Adulthood: A Longitudinal Study of Women.

INTRODUCTION: Smoking cessation is more than 50% heritable. Genetic studies of smoking cessation have been limited by short-term follow-up or cross-sectional design. AIMS AND METHODS: This study tests single nucleotide polymorphism (SNP) associations with cessation during long-term follow-up throughout adulthood in women. The secondary aim tests whether genetic associations differ by smoking intensity. Associations between 10 SNPs in CHRNA5, CHRNA3, CHRNB2, CHRNB4, DRD2, and COMT and the probability of smoking cessation over time were evaluated in two longitudinal cohort studies of female nurses, the Nurses' Health Study (NHS) (n = 10 017) and NHS-2 (n = 2793). Participant follow-up ranged from 2 to 38 years with data collected every 2 years. RESULTS: Women with the minor allele of either CHRNA5 SNP rs16969968 or CHRNA3 SNP rs1051730 had lower odds of cessation throughout adulthood [OR = 0.93, p-value = .003]. Women had increased odds of cessation if they had the minor allele of CHRNA3 SNP rs578776 [OR = 1.17, p-value = .002]. The minor allele of DRD2 SNP rs1800497 was associated with lower odds of cessation in moderate-to-heavy smokers [OR = 0.92, p-value = .0183] but increased odds in light smokers [OR = 1.24, p-value = .096]. CONCLUSIONS: Some SNP associations with short-term smoking abstinence observed in prior studies were shown in the present study to persist throughout adulthood over decades of follow-up. Other SNP associations with short-term abstinence did not persist long-term. The secondary aim findings suggest genetic associations may differ by smoking intensity. IMPLICATIONS: The results of the present study expand on previous studies of SNP associations in relation to short-term smoking cessation to demonstrate some of these SNPs were associated with smoking cessation throughout decades of follow-up, whereas other SNP associations with short-term abstinence did not persist long-term. The rate of relapse to smoking remains high for several years after quitting smoking, and many smokers experience multiple quit attempts and relapse episodes throughout adulthood. Understanding genetic associations with long-term cessation has potential importance for precision medicine approaches to long-term cessation management.

Remote Carbon Monoxide Capture via REDCap: Evaluation of an Integrated Mobile Application.

INTRODUCTION: To improve the feasibility of remote biochemical verification of smoking status, our team developed "COast", a mobile app integrated with REDCap that allows a research participant to complete self-report research assessments and provide a breath sample via the iCOQuit® Smokerlyzer® for the purposes of carbon monoxide (CO) testing. The aims of the present study were to examine: 1) the validity of remote CO data capture using COast as compared to gold standard approaches (salivary cotinine, stand-alone CO monitor) and 2) the feasibility of remote CO data capture using COast as applied to both daily and weekly CO collection schedules. METHODS: Participants (N=143, 59% Female), including recently quit (n=36) and current (n=107) smokers, completed a baseline video session to capture validity data, and then were randomized to daily or weekly CO monitoring for a period of one month. RESULTS: Balancing both sensitivity and specificity, optimal cut-points for defining abstinence using the COast system were < 4 parts per million (ppm) with salivary cotinine as the referent (Sensitivity = 100%, Specificity = 92.8%) and < 8ppm with the stand-alone CO monitor as the referent (Sensitivity = 100%, Specificity = 88.9%). Compliance across groups with CO monitoring was high with average compliance of 74% for the daily group and 84% for the weekly group. Self-reported feasibility and acceptability of using the system were strong. CONCLUSIONS: Pairing the iCOQuit with REDCap via the COast app was both valid and feasible among a sample of adults who smoke cigarettes enrolled remotely. This integration may help to improve the rigor of decentralized smoking cessation trials. IMPLICATIONS: With increasing prevalence of decentralized trial designs, innovative methods are needed to remotely capture biomarkers. Methods that leverage existing widely available research data capture platforms may be particularly useful for promoting adoption. The COast app, which integrates a Bluetooth-enabled carbon monoxide monitor with REDCap, is a fitting, valid, feasible solution to remotely biochemically verify smoking status.

A Secondary Analysis of a Preliminary Contingency Management Intervention for Presurgical Cancer Patients: Evaluating Individual Participant Data.

INTRODUCTION: Contingency management (CM) interventions deliver monetary reinforcers contingent upon biochemically verified abstinence from smoking. CM has been found to be effective, however, individual participant, analyses are warranted to further elucidate how individual-level behavior patterns vary during the intervention period, both within and across treatment groups. AIMS AND METHODS: This is a secondary analysis of a randomized controlled pilot trial of presurgical cancer patients who smoke (RCT N = 40). All participants were current everyday smokers and were enrolled in cessation counseling, offered nicotine replacement therapy, and submitted breath CO testing 3 times per week for 2-5 weeks. Participants randomized to CM received monetary reinforcers for breath CO ≤6 ppm on an escalating schedule of reinforcement with a reset for positive samples. Sufficient breath CO data exist for 28 participants (CM = 14; monitoring only [MO] = 14). Effect size was calculated for differences in negative CO tests. Time to first negative test was tested using survival analysis. Fisher's exact test was used to assess relapse. RESULTS: The CM group achieved abstinence more quickly (p < .05), had a lower percentage of positive tests (h = 0.80), and experienced fewer lapses following abstinence (p = .00). While 11 of 14 participants in the CM group achieved and sustained abstinence by their third breath test, this was only true for 2 of the 14 MO participants. CONCLUSIONS: Those in CM achieved abstinence quicker and with fewer lapses than those engaged in MO speaking to the efficacy of the schedule of financial reinforcement. This is particularly important within presurgical populations given the potential benefits to postoperative cardiovascular and wound infection risk. IMPLICATIONS: While the efficacy of CM as an intervention is well established, this secondary analysis provides insight into the individual behavior patterns underlying successful abstinence. Those assigned to CM were not only more likely to achieve abstinence, but did so more quickly and with fewer instances of relapse. This is of particular importance to those scheduled for surgery where achieving abstinence as early as possible impacts on the risk of postoperative complications. CM interventions may be particularly well suited for critical windows in which timely and sustained abstinence is advantageous.

Interest in quitting e-cigarette use by device type and smoking history in US adults.

BACKGROUND: The use of e-cigarettes has been increasing, especially since the introduction of 'pod' devices to the marketplace since 2018. Most adults who vape report interest in quitting. The present study examined level of interest in e-cigarette cessation between users with varying cigarette smoking histories and device types. METHODS: Data obtained from wave 5 (2018-2019) of the Population Assessment of Tobacco and Health study (n=34 309). Analyses were conducted on adult current established e-cigarette users, categorised on cigarette smoking history (current, former or never) and device type (disposable, cartridge/pod, tank or mod). Participants reported if they planned to ever quit e-cigarettes, attempted to quit in the past year and attempted to quit by cutting back in the past year. RESULTS: Of the 2922 established e-cigarette users, 68.21% reported plans to quit vaping; 17.27% reported attempting to quit e-cigarettes in the past year; and 29.28% reported attempting to quit by cutting back in the past year. Cartridge users had higher odds of interest in quitting than tank and mod users. Disposable and cartridge users had higher odds of reporting a past year quit attempt than tank and mod users. Individuals with no smoking history had higher odds of reporting a past year quit attempt or cutting back relative to those reporting dual use (of both e-cigarettes and cigarettes) and former smoking. CONCLUSIONS: Tobacco control should consider the type of e-cigarette device that is being used, alongside users' cigarette smoking history, when developing interventions and other resources for vaping cessation.

Behavioral Activation-Based Digital Smoking Cessation Intervention for Individuals With Depressive Symptoms: Randomized Clinical Trial.

BACKGROUND: Depression is common among adults who smoke cigarettes. Existing depression-specific cessation interventions have limited reach and are unlikely to improve smoking prevalence rates among this large subgroup of smokers. OBJECTIVE: This study aimed to determine whether a mobile app-based intervention tailored for depression paired with a mailed sample of nicotine replacement therapy (NRT) is efficacious for treating depression and promoting smoking cessation. METHODS: A 2-arm nationwide remote randomized clinical trial was conducted in the United States. Adults (N=150) with elevated depressive symptoms (Patient Health Questionnaire-8≥10) who smoked were enrolled. The mobile app ("Goal2Quit") provided behavioral strategies for treating depression and quitting smoking based on Behavioral Activation Treatment for Depression. Goal2Quit participants also received a 2-week sample of combination NRT. Treatment as usual participants received a self-help booklet for quitting smoking that was not tailored for depression. Primary end points included Goal2Quit usability, change in depression (Beck Depression Inventory-II) across 12 weeks, and smoking cessation including reduction in cigarettes per day, incidence of 24-hour quit attempts, floating abstinence, and 7-day point prevalence abstinence (PPA). RESULTS: In total, 150 participants were enrolled between June 25, 2020, and February 23, 2022, of which 80 were female (53.3%) and the mean age was 38.4 (SD 10.3) years. At baseline, participants on average reported moderate depressive symptoms and smoked a mean of 14.7 (SD 7.5) cigarettes per day. Goal2Quit usability was strong with a mean usability rating on the System Usability Scale of 78.5 (SD 16.9), with 70% scoring above the ≥68 cutoff for above-average usability. Retention data for app use were generally strong immediately following trial enrollment and declined in subsequent weeks. Those who received Goal2Quit and the NRT sample reported lower mean depressive symptoms over the trial duration as compared to treatment as usual (difference of mean 3.72, SE 1.37 points less; P=.01). Across time points, all cessation outcomes favored Goal2Quit. Regarding abstinence, Goal2Quit participants reported significantly higher rates of 7-day PPA at weeks 4 (11% vs 0%; P=.02), 8 (7-day PPA: 12% vs 0%; P=.02), and 12 (16% vs 2%; P=.02). CONCLUSIONS: A mobile app intervention tailored for depression paired with a sample of NRT was effective for depression treatment and smoking cessation. Findings support the utility of this intervention approach for addressing the currently unmet public health treatment need for tailored, scalable depression-specific cessation treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT03837379; https://clinicaltrials.gov/ct2/show/NCT03837379.

The Cost-Effectiveness of Nicotine Replacement Therapy Sampling in Primary Care: a Markov Cohort Simulation Model.

BACKGROUND: Pharmacotherapies remain a central focus of successful tobacco control, but uptake remains very low. OBJECTIVE: To estimate the cost effectiveness of a primary care nicotine replacement therapy (NRT) sampling intervention. DESIGN: A Markov cohort simulation model was constructed to conduct cost-effectiveness analyses. Clinical trial results were used to initialize the Markov model. All other model parameters were derived from the literature. The study was conducted over a lifetime horizon, from the payers' budgetary perspective. PARTICIPANTS: Smokers with a primary care visit. INTERVENTION: Medication sampling, which provided short, starter packets of NRT (nicotine patch and lozenge) to smokers in the primary care setting. MAIN MEASURES: Lifetime healthcare expenditures, quality-adjusted life years, and life years. KEY RESULTS: Medication sampling was the dominant strategy compared to standard care. Our intervention cost $75, yielding a discounted lifetime savings of $1065 in healthcare expenditures, and increased both discounted quality-adjusted life years and discounted life years by 0.01. One-way sensitivity analyses showed that medication sampling remained dominant in plausible ranges except when it failed to increase cessation relative to standard care. Probabilistic sensitivity analyses confirmed that medication sampling was dominant in 94.1% of the simulated cases, with an implementation cost of $74 (95% CI $73-$76) and discounted lifetime savings in health expenditures of $1061 (- $1106 to - $1,017), increasing quality-adjusted life years by 0.008 (0.0085-0.0093) and life years by 0.008 (0.0081-0.0089). CONCLUSION: Medication sampling, an easily implementable, scalable and low-cost intervention to encourage smoking cessation, is cost saving and improves quality of life.

Nicotine Metabolism Predicted by CYP2A6 Genotypes in Relation to Smoking Cessation: A Systematic Review.

INTRODUCTION: Identifying genetic factors associated with smoking cessation could inform precision cessation interventions. Of major interest is genetic variation in nicotine metabolism, largely predicted by CYP2A6 variations. AIMS AND METHODS: We conducted a systematic literature review to summarize the population-based evidence of the association between CYP2A6 and smoking cessation. In the 12 studies meeting the inclusion criteria, the known functional metabolic effect of CYP2A6 variants was used to classify nicotine metabolism as normal (>75% metabolic activity), intermediate (50.1%-75% activity), slow (25%-50% activity), and poor (<25% activity). Summary odds ratios of smoking cessation were calculated across metabolic groups, stratified by ancestry and whether participants received pharmacotherapy or placebo/no treatment. RESULTS: Among untreated people of European ancestry (n = 4 studies), those with CYP2A6 reduced metabolism were more likely to quit smoking than those with normal metabolism (Summary OR = 2.05, 95% CI 1.23 to 3.42) and the likelihood of cessation increased as nicotine metabolism decreased. Nicotine replacement therapy attenuated the association at end-of-treatment, while bupropion modified the association such that intermediate/slow metabolizers were less likely to quit than normal metabolizers (Summary OR = 0.86, 95% CI 0.79 to 0.94). Among untreated Asian people (n = 3 studies), results differed compared with those with European ancestry: those with slow metabolism were less likely to have quit smoking than normal metabolizers (Summary OR = 0.52, 95% CI 0.38 to 0.71). Evidence for people of African ancestry (n = 1 study) suggested the CYP2A6 association with cessation may differ compared with those of European ancestry. CONCLUSIONS AND IMPLICATIONS: Most studies included in this review were of European ancestry populations; these showed slower nicotine metabolism was associated with increased likelihood of smoking cessation in a dose-related manner. Pharmacotherapy appeared to attenuate or modify this association among people of European ancestry, but it is unclear whether the change in the association remains consistent after treatment ceases. This finding has implications for precision medicine cessation interventions. Based on only a few studies of people of Asian or African ancestry, the association between CYP2A6 variants and cessation may differ from that observed among those of European ancestry, but more evidence is needed.

A Daily Assessment Study of Smoking Cessation After a Head and Neck Cancer Diagnosis.

INTRODUCTION: This intensive longitudinal study describes key events in the process of smoking cessation after a new head and neck cancer (HNC) diagnosis. Prior longitudinal studies show some cancer patients quit, while others continue to smoke, but details about the pattern in which these discrete outcomes arise are scarce. This study is meant to help rectify this gap in the literature. AIMS AND METHODS: Participants were 42 HNC patients who reported current smoking at enrollment. Participants were recruited from an outpatient oncology clinic and completed a baseline questionnaire prior to begin a 30-day daily assessment. RESULTS: Few participants (9.52%) achieved 30-day continuous abstinence from smoking. On average, participants reported 9.64 ± 11.93 total days of abstinence. Nearly, all (94.44%, n = 34) participants made at least one quit attempt, with an average of 16.94 ± 11.30 quit attempt days. Fewer participants were able to achieve a 24-hour quit attempt (52.78%, n = 19), with a corresponding average of 5.50 ± 8.69 24-hour days. The median time to first 24-hour quit attempt was 13 days after enrollment. Based on smoking behavioral patterns, participants were categorized into five groups, the most common being "persistent attempters," which involved unsuccessful quit attempts throughout the study. Only 45% of participants (n = 19) used evidence-based treatment, the most common being cessation medication. CONCLUSIONS: This intensive longitudinal study found that cancer diagnosis can spur a lot of efforts to quit smoking. Unfortunately, this study suggests that many quit attempts are short lived, possibly a result of an absence or insufficient use of evidence-based treatments. IMPLICATIONS: For adults who are current smokers at the time of cancer diagnosis, there is a high likelihood of persistent cigarette smoking and use of other tobacco products in the weeks and months after a cancer diagnosis. Furthermore, this study shows that while a lot of quit attempts may occur, few are successful, which may be partly attributable to the low use of evidence-based tobacco treatment. Future research with cancer patients should aim to identify predictors of quit attempts and abstinence as well as treatment utilization.

Characterization of Salivary Progesterone in Female Smokers.

INTRODUCTION: Fluctuations in ovarian hormones have been associated with changes in cigarette smoking behavior, which can be measured through both serum or less invasive salivary procedures. The primary aim of this exploratory study is to characterize the progesterone profiles of salivary progesterone measurements and to compare that with the profiles estimated from a previously measured serum sample. AIMS AND METHODS: Nontreatment-seeking, cigarette smoking women (n = 82; ages 18-45 years) provided daily salivary hormone samples every morning for 14 consecutive days. Time-dependent random effects functions were used to approximate daily salivary progesterone (ng/mL) levels over the course of a standardized menstrual cycle. Serum measures of progesterone from a previous study of female cigarette smokers were examined for consistency with established profiles and compared with the salivary profile using the same methodology. RESULTS: The salivary model fit exhibits relative stability during the follicular phase and a clear unimodal peak during the luteal phase. Parameter estimates from the non-linear function show correspondence to serum data. Although the profiles estimated from salivary and serum data agree in functional form, we observed larger between-subject heterogeneity both in the follicular level and the peak luteal level in salivary measures. CONCLUSIONS: The pattern of salivary and serum progesterone measured across the menstrual cycle is similar in form, which is noteworthy given that the saliva and serum samples were drawn from independent sample of female smokers. Inter- and intra-individual variation in salivary measures may be greater than in serum measures. IMPLICATIONS: Measuring progesterone level variation across the menstrual cycle via saliva samples has several benefits relative to serum sampling methods in that they are easily obtained, noninvasive, and low-cost. Inter- and intra-individual variation in measurements may be greater than those in serum measurements. However, the functional form of the salivary progesterone profile is isomorphic to serum progesterone.

Reappraising Choice in Addiction: Novel Conceptualizations and Treatments for Tobacco Use Disorder.

The introduction of alternative nicotine and tobacco products (such as e-cigarettes, heat-not-burn devices, nicotine pouches) warrants an updated framework from which to conceptualize tobacco use disorder (TUD). The following review provides considerations for TUD within the context of novel products. Historically, the tobacco industry falsely claimed that cigarettes were not addictive or harmful and that those who smoked simply chose to do so. This generated an inaccurate lay perception that smoking is a free or informed choice. Research on nicotine pharmacology demonstrates the powerful addictive potential of nicotine, which is shaped by dose, speed of delivery, and other constituents generated. In addition, non-pharmacologic reinforcers motivate and maintain tobacco use behaviors for both traditional cigarettes and novel products. The negative consequences of combustible tobacco use are well known; however, these outcomes may differ for alternative products. Strategies used for combustible product cessation may be adapted for novel products, and treatment recommendations for TUD should be made within the context of a harm reduction framework wherein alternative product use may be the desired outcome. Providers must therefore be willing to modify their perceptions of products and treatment recommendations accordingly. Better public health outcomes are accomplished through promotion of abstinence from combustible smoking. For those who cannot wean from nicotine entirely, switching to less risky modes of delivery might be a secondary goal, with an eventual aim of stopping use of the alternative product. Implications: Given the advent of novel, alternative tobacco products, tobacco use disorder (TUD) must be conceptualized within a contemporary framework that includes harm reduction and alternative outcomes. The unique contributions of nicotine pharmacology, non-pharmacologic reinforcers, and consequences of use can be used to inform treatments for TUD with the ultimate goal of improving the health of individuals who use tobacco.

Early Changes in Puffing Intensity When Exclusively Using Open-Label Very Low Nicotine Content Cigarettes.

INTRODUCTION: In response to reducing cigarette nicotine content, people who smoke could attempt to compensate by using more cigarettes or by puffing on individual cigarettes with greater intensity. Such behaviors may be especially likely under conditions where normal nicotine content (NNC) cigarettes are not readily accessible. The current within-subject, residential study investigated whether puffing intensity increased with very low nicotine content (VLNC) cigarette use, relative to NNC cigarette use, when no other nicotine products were available. AIMS AND METHODS: Sixteen adults who smoke daily completed two four-night hotel stays in Charleston, South Carolina (United States) in 2018 during which only NNC or only VLNC cigarettes were accessible. We collected the filters from all smoked cigarettes and measured the deposited solanesol to estimate mouth-level nicotine delivery per cigarette. These estimates were averaged within and across participants, per each 24-h period. We then compared the ratio of participant-smoked VLNC and NNC cigarette mouth-level nicotine with the ratio yielded by cigarette smoking machines (when puffing intensity is constant). RESULTS: Average mouth-level nicotine estimates from cigarettes smoked during the hotel stays indicate participants puffed VLNC cigarettes with greater intensity than NNC cigarettes in each respective 24-h period. However, this effect diminished over time (p < .001). Specifically, VLNC puffing intensity was 40.0% (95% CI: 29.9, 53.0) greater than NNC puffing intensity in the first period, and 16.1% (95% CI: 6.9, 26.0) greater in the fourth period. CONCLUSION: Average puffing intensity per cigarette was elevated with exclusive VLNC cigarette use, but the extent of this effect declined across four days. IMPLICATIONS: In an environment where no other sources of nicotine are available, people who smoke daily may initially attempt to compensate for cigarette nicotine reduction by puffing on individual cigarettes with greater intensity. Ultimately, the compensatory behavior changes required to achieve usual nicotine intake from VLNC cigarettes are drastic and unrealistic. Accordingly, people are unlikely to sustain attempts to compensate for very low cigarette nicotine content.

Proactive Electronic Visits for Smoking Cessation and Chronic Obstructive Pulmonary Disease Screening in Primary Care: Randomized Controlled Trial of Feasibility, Acceptability, and Efficacy.

BACKGROUND: Most smokers with chronic obstructive pulmonary disease (COPD) have not yet been diagnosed, a statistic that has remained unchanged for over two decades. A dual-focused telehealth intervention that promotes smoking cessation, while also facilitating COPD screening, could help address national priorities to improve the diagnosis, prevention, treatment, and management of COPD. The purpose of this study was to preliminarily evaluate an integrated asynchronous smoking cessation and COPD screening e-visit (electronic visit) that could be delivered proactively to adult smokers at risk for COPD, who are treated within primary care. OBJECTIVE: The aims of this study were (1) to examine e-visit feasibility and acceptability, particularly as compared to in-lab diagnostic pulmonary function testing (PFT), and (2) to examine the efficacy of smoking cessation e-visits relative to treatment as usual (TAU), all within primary care. METHODS: In a randomized clinical trial, 125 primary care patients who smoke were randomized 2:1 to receive either proactive e-visits or TAU. Participants randomized to the e-visit condition were screened for COPD symptoms via the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE). Those with scores ≥2 were invited to complete both home spirometry and in-lab PFTs, in addition to two smoking cessation e-visits. Smoking cessation e-visits assessed smoking history and motivation to quit and included completion of an algorithm to determine the best Food and Drug Administration-approved cessation medication to prescribe. Primary outcomes included measures related to (1) e-visit acceptability, feasibility, and treatment metrics; (2) smoking cessation outcomes (cessation medication use, 24-hour quit attempts, smoking reduction ≥50%, self-reported abstinence, and biochemically confirmed abstinence); and (3) COPD screening outcomes. RESULTS: Of 85 participants assigned to the e-visits, 64 (75.3%) were invited to complete home spirometry and in-lab PFTs based on CAPTURE. Among those eligible for spirometry, 76.6% (49/64) completed home spirometry, and 35.9% (23/64) completed in-lab PFTs. At 1 month, all cessation outcomes favored the e-visit, with a significant effect for cessation medication use (odds ratio [OR]=3.22). At 3 months, all cessation outcomes except for 24-hour quit attempts favored the e-visit, with significant effects for cessation medication use (OR=3.96) and smoking reduction (OR=3.09). CONCLUSIONS: A proactive, asynchronous e-visit for smoking cessation and COPD screening may offer a feasible, efficacious approach for broad interventions within primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04155073; https://clinicaltrials.gov/ct2/show/NCT04155073.

A Preoperative Contingency Management Intervention for Smoking Abstinence in Cancer Patients: A Preliminary Randomized Controlled Trial.

INTRODUCTION: The purpose of this study was to evaluate a pilot preoperative contingency management (CM) intervention for smoking abstinence. AIMS AND METHODS: This multisite pilot study was conducted at two cancer center-based tobacco treatment programs. Participants who were smoking, diagnosed with or suspected to have any type of operable cancer, and had a surgical procedure scheduled in the next 10 days to 5 weeks (N = 40) were randomized to receive standard care plus monitoring only (MO) or CM prior to surgery. All patients received breath carbon monoxide (CO) tests 3 times per week, nicotine patches, and counseling. The CM group also earned payments for self-reported smoking abstinence confirmed by CO breath test ≤6 ppm on an escalating schedule of reinforcement (with a reset if they smoked). Seven-day point prevalence abstinence rates on the day of surgery and at 3-month follow-up were compared between groups using repeated measures log-linear regression models utilizing generalized estimating equations. Participants lost to follow-up are assumed to have returned to smoking. RESULTS: The sample was 50% female and 75% White. In covariate adjusted models, patients in the CM group had a greater probability of reported abstinence. On the day of surgery (end of treatment), 52% of CM patients were abstinent compared with 16% of patients in MO (risk ratio = 3.2 [1.1-9.3]; p = .03). At the 3-month follow-up, 43% of CM patients were abstinent compared with 5% in MO (risk ratio = 8.4 [1.5-48.3]; p = .02). CONCLUSIONS: Providing monetary incentives contingent on abstinence prior to cancer surgery may produce significant improvements in smoking abstinence rates relative to breath CO MO. IMPLICATIONS: In this pilot preoperative CM intervention for smoking abstinence, patients receiving a CM intervention prior to cancer surgery had a greater probability of smoking abstinence at the end of treatment compared with a breath MO group (52% vs. 16%, respectively). Thus, providing monetary incentives contingent on abstinence may produce significant improvements in smoking abstinence rates prior to cancer surgery relative to breath CO monitoring.

A Pilot Study of Nicotine Replacement Therapy Sampling and Selection to Increase Medication Adherence in Low-Income Smokers.

INTRODUCTION: Adherence to smoking cessation medications remains suboptimal, particularly among low-income smokers. Guided, experiential sampling of nicotine replacement therapies (NRTs) may increase NRT adherence and smoking cessation over gold standard counseling plus NRT. The present pilot study aimed to examine feasibility, acceptability, and preliminary efficacy of a novel experiential intervention. AIMS AND METHODS: This pilot randomized controlled trial (N = 83) compared gold standard smoking cessation treatment (four weekly sessions of behavioral counseling followed by self-selected combination NRT in week 5) to a novel experiential approach (ie, In Vivo; four weekly sessions of sampling each short form of NRT-gum, lozenge, inhaler, nasal spray-in-session while wearing the nicotine patch followed by NRT selection in week 5). Both groups received 8 weeks of nicotine patch plus their selected additional short form NRT for smoking cessation followed by a 1-month assessment. RESULTS: Screening and enrollment rates supported feasibility. In Vivo was comparable in acceptability with the gold standard of care intervention; however, there was greater attrition in the In Vivo group compared with the gold standard of care group. Results suggested higher medication adherence and improvements in smoking behavior in the In Vivo intervention; with generally small-to-medium effect sizes. CONCLUSIONS: This experiential approach to sampling NRT is feasible and acceptable to low-income people who smoke. This intervention may increase adherence and reduce harmful smoking behavior but needs to be tested on a larger scale. IMPLICATIONS: Medication adherence remains a significant impediment to the successful smoking cessation. The results of this study suggest that guided sampling of NRT products improves adherence among low-income smokers. Additionally, this approach yielded greater improvements in smoking behavior compared with gold standard smoking cessation treatment. This intervention shows promise as a feasible smoking cessation treatment for low-income smokers.

A Pilot Randomized Clinical Trial of Remote Varenicline Sampling to Promote Treatment Engagement and Smoking Cessation.

INTRODUCTION: Medication sampling is a clinically useful tool to engage smokers in the quitting process. Whether varenicline is suitable for sampling purposes is unclear. The purpose of this study was to examine the feasibility, uptake, and preliminary outcomes of varenicline sampling. METHODS: Smokers (N = 99), both motivated to quit and not, were recruited and randomized to varenicline sampling versus not, with 12 week follow-up. The intervention consisted of mailing one-time samples of varenicline (lasting 2-4 wks), with minimally suggestive guidance on use. RESULTS: Uptake of varenicline was strong, at 2 weeks (54% any use, 66% daily use) and 4 weeks (38%, 46%), with 58% of medication users seeking additional medication. Most users followed conventional titration patterns, self-titrating from 0.5 mg to 2 mg. Relative to control, varenicline sampling increased motivation (p = 0.006) and confidence to quit (p = 0.02), and decreased cigarette smoking (p = 0.02). Smokers receiving varenicline samples were significantly more likely to achieve 50% reduction in cigarettes per day (CPD), both immediately following the sampling exercise (Adjusted Odds Ratio [AOR] = 4.12; 95% CI: 1.39 to 12.17) and at final follow-up (AOR = 4.50; 95% CI: 1.56 to 13.01). Though cessation outcomes were not statistically significant, there was a 1.5 to 3-fold increase in quit attempts and abstinence from varenicline sampling throughout follow-up. These outcomes were comparable among smokers motivated to quit and not. CONCLUSIONS: Unguided, user-driven sampling of varenicline sampling is a concrete behavioral exercise that is feasible to do and seems to suggest clinical utility. Sampling is a pragmatic clinical approach to engage more smokers in quitting. IMPLICATIONS: Use of evidence-based pharmacotherapies for smoking cessation is low. Medication sampling is a pragmatic behavioral exercise that allows smokers to experience the benefits of using them, while promoting positive downstream effects towards quitting. While previous studies have shown that nicotine replacement therapy (NRT) sampling is viable and effective, whether this extends to varenicline is unclear. Results from this trial demonstrate that varenicline sampling is feasible, safe, and suggestive of clinically important steps toward quitting, deserving of a larger trial. CLINICAL TRIAL REGISTRATION: NCT #03742154.

Increases in endogenous progesterone attenuate smoking in a cohort of nontreatment seeking women: An exploratory prospective study.

Despite advances in prevention and treatment, cigarette smoking remains a leading cause of preventable death in the United States. Although men and women are equally likely to attempt to quit smoking cigarettes, women are far less likely to achieve abstinence both during and following cessation treatment. Recent evidence suggests that ovarian hormone levels may play a role in successful abstinence attempts in women smokers. The primary goal of this exploratory prospective observational study was to estimate the association between within-participant levels of progesterone and estradiol with associated cigarettes smoked per day in adult women smokers (n = 104). The primary study outcome was self-reported cigarettes smoked per day (CPD) during a 2-week observational period collected using a daily smoking diary. Additionally, participants collected saliva daily, from which hormone levels (progesterone and estradiol) were derived. Higher within-participant progesterone levels were associated with a significant decrease in CPD (p = .008) whereas within-participant estradiol levels were unrelated to CPD (p = .25). Regression models indicated a single change in the trajectory of smoking behavior for both within-participant progesterone and estradiol. When progesterone values were below the change point, there was a significant inverse relationship between within-participant progesterone levels and smoking behavior (p = .025) whereas the relationship was attenuated for higher within-participant progesterone levels (p = .59). The effect of estradiol on smoking behavior was not significant when it was either below (p = .92) or above (p = .16) the change point. Higher within-participant levels of progesterone but not estradiol are associated with reduced CPD in nontreatment seeking women smokers.

Evaluation of a Proactive Smoking Cessation Electronic Visit to Extend the Reach of Evidence-Based Cessation Treatment via Primary Care.

Background:Best practice guidelines for smoking cessation treatment through primary care advise the 5As model. However, compliance with these guidelines is poor, leaving many smokers untreated. The purpose of this study was to develop and preliminarily evaluate an asynchronous smoking cessation electronic visit (e-visit) that could be delivered proactively through the electronic health record (EHR) to adult smokers treated within primary care. The goal of the e-visit is to automate 5As delivery to ensure that all smokers receive evidence-based cessation treatment. As such, the aims of this study were twofold: (1) to examine acceptability, feasibility, and treatment metrics associated with e-visit utilization and (2) to preliminarily examine efficacy relative to treatment as usual (TAU) within primary care.Methods:Participants (n = 51) were recruited from primary care practices between November 2018 and October 2019 and randomized 2:1 to receive either the smoking cessation e-visit or TAU. Participants completed assessments of cessation outcomes 1-month and 3-months postenrollment and e-visit analytics data were gathered from the EHR.Results:Self-report feedback from e-visit participants indicated satisfaction with the intervention and interest in using e-visits again in the future. Nearly all e-visits resulted in prescription of a U.S. Food and Drug Administration (FDA)-approved smoking cessation medication. In general, smoking cessation outcomes favored the e-visit condition at both 1 (odds ratios [ORs]: 2.10-5.39) and 3 months (ORs: 1.31-4.67).Conclusions:These results preliminarily indicate the feasibility, acceptability, and efficacy of this smoking cessation e-visit within primary care. Future studies should focus on larger scale examination of effectiveness and implementation across settings. The clinicaltrials.gov registration number for this trial is NCT04316260.

The differential impact of nicotine replacement therapy sampling on cessation outcomes across established tobacco disparities groups.

Cigarette smoking is increasingly concentrated among marginalized populations with limited access to evidence-based cessation treatment. This includes racial/ethnic minorities, lower income individuals, those with lower educational attainment, and residents of rural areas. To reach Healthy People 2020 objectives, successful cessation interventions must narrow these disparities. Nicotine replacement therapy (NRT) sampling is an easily translatable and scalable intervention that could enhance treatment access and thus narrow disparities. The present study examined individual-level demographic moderators of the impact of NRT sampling on cessation-related behaviors including: 1) use of a cessation medication, 2) making a 24-hour quit attempt, 3) floating abstinence, and 4) 7-day point prevalence abstinence at 6-months. Study participants included N = 1245 adult smokers enrolled in the Tobacco Intervention in Primary Care Treatment Opportunities for Providers (TIP TOP) study, a recently concluded large-scale clinical trial of NRT sampling relative to standard care within 22 primary care clinics across South Carolina. Generalized linear models examined individual-level demographic moderators of treatment effect. Results suggest that NRT sampling may be more effective among some of the most disadvantaged groups of smokers, including smokers with lower income and education, as well those who live in more rural areas. The effects of NRT sampling did not differ by race. In sum, NRT sampling is a low-cost, low-burden intervention that could be disseminated broadly to reach large numbers of smokers and potentially narrow cessation disparities.